- PYRROLOPYRIMIDINE ITK INHIBITORS
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Disclosed herein are arylpyridinone compounds and compositions useful in the treatment of ITK mediated diseases, such as inflammation, having the structures of Formulas (I)-(IV): wherein the R groups, m, n, and X are as defined in the detailed description. Methods of inhibition of ITK activity in a human or animal subject are also provided.
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- IRAK DEGRADERS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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Paragraph 00962; 001299-001301
(2020/06/19)
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- IRAK4 kinase inhibitor and preparation method thereof
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The invention provides a compound with a general formula I, and a pharmaceutically acceptable salt, a stereoisomer, an ester, a prodrug, a solvate and a deuterated compound thereof, wherein the compound is an IRAK4 kinase inhibitor and can be used for pre
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Paragraph 0107-0111; 0124-0128; 0141-0145
(2020/09/23)
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- PYRROLOTRIAZINONE DERIVATIVES AS PI3K INHIBITORS
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New pyrrolotriazinone derivatives having the chemical structure of formula (I), are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Phosphoinositide 3-Kinases (PI3Ks)
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- Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing
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Pyrazolopyridine inhibitors with low micromolar potency for CHK1 and good selectivity against CHK2 were previously identified by fragment-based screening. The optimization of the pyrazolopyridines to a series of potent and CHK1-selective isoquinolines demonstrates how fragment-growing and scaffold morphing strategies arising from a structure-based understanding of CHK1 inhibitor binding can be combined to successfully progress fragment-derived hit matter to compounds with activity in vivo. The challenges of improving CHK1 potency and selectivity, addressing synthetic tractability, and achieving novelty in the crowded kinase inhibitor chemical space were tackled by multiple scaffold morphing steps, which progressed through tricyclic pyrimido[2,3-b] azaindoles to N-(pyrazin-2-yl)pyrimidin-4-amines and ultimately to imidazo[4,5-c]pyridines and isoquinolines. A potent and highly selective isoquinoline CHK1 inhibitor (SAR-020106) was identified, which potentiated the efficacies of irinotecan and gemcitabine in SW620 human colon carcinoma xenografts in nude mice. (Figure presented)
- Reader, John C.,Matthews, Thomas P.,Klair, Suki,Cheung, Kwai-Ming J.,Scanlon, Jane,Proisy, Nicolas,Addison, Glynn,Ellard, John,Piton, Nelly,Taylor, Suzanne,Cherry, Michael,Fisher, Martin,Boxall, Kathy,Burns, Samantha,Walton, Michael I.,Westwood, Isaac M.,Hayes, Angela,Eve, Paul,Valenti, Melanie,De Haven Brandon, Alexis,Box, Gary,Van Montfort, Rob L. M.,Williams, David H.,Aherne, G. Wynne,Raynaud, Florence I.,Eccles, Suzanne A.,Garrett, Michelle D.,Collins, Ian
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p. 8328 - 8342
(2012/02/06)
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- MORPHOLINO-SUBSTITUTED BICYCLOHETEROARYL COMPOUNDS AND THEIR USE AS ANTI CANCER AGENTS
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The present invention pertains generally to the field of therapeutic compounds, and mor specifically to certain morpholino-substituted bicydoheteroaryl compounds (referred to herein as MBHA compounds), of the following formula: and especially certain morp
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Page/Page column 82
(2008/12/06)
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